Noninferiority of three months versus six months of oxaliplatin-based adjuvant chemotherapy for resected colon cancer. How should IDEA findings affect clinical practice?

Abstract

The eagerly awaited results of the multi-continental International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project have recently been presented at major oncological meetings. The 3-year disease-free survival (DFS) was presented for 12,834 Stage III colon cancer patients in a pooled analysis of 6 individual noninferiority phase III randomized trials, all investigating three versus six months of oxaliplatin-based adjuvant therapy. Noninferiority (NI) could not be demonstrated for the whole population as the DFS hazard ratio (HR) of 1.07 with its 95% CI of 1.00–1.15 crossed the postulated NI boundary of 1.12. However, there was an expected reduction in the incidence of specific side effects with the three months treatment. NI could be demonstrated for the T3N1 subgroup (∼60% of patients, HR for DFS 1.01, 95% CI 0.90–1.12). Moreover, NI was also declared for the subgroup treated with the CAPOX regimen (capecitabine plus oxaliplatin, ∼40% of patients), but the CAPOX choice was physician-based and not subject to randomization. Overall, the IDEA results indicate that three months of therapy might be adequate for most of Stage III tumors; however, a small subset of these patients still have high risk of recurrence and death with short treatment duration. Precise predictors of benefit need to be identified, nonetheless tumor-intrinsic factors, such as tumor stage, might currently be considered as useful tools to inform the decision-making process.